HTD1801, is a first-in-class anti-inflammatory metabolic modulator that activates AMPK and inhibits the NLRP3 inflammasome. These pathways converge at the nexus of metabolic dysregulation beyond glucose control and chronic inflammation. This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of HTD1801 compared to placebo in patients with T2DM inadequately controlled with metformin. The primary endpoint of Symphony 2 was change from baseline in HbA1c to Week 24 compared to placebo. Secondary endpoints explored effects on cardiovascular, metabolic, and renal comorbidities to assess it’s potential as a comprehensive Cardiovascular-Kidney-Metabolic therapy.

Eligible patients were randomized 2:1 to HTD1801 1000 mg BID (N=365) or placebo (N=184). The study met the primary endpoint at Week 24, with HTD1801-treated patients achieving an LS mean change in HbA1c of -1.21% compared to ‑0.68% with placebo (LS mean diff: -0.53, p<0.0001). 33% of HTD1801-treated patients achieved HbA1c <7% at Week 24 vs 11% with placebo (p<0.0001). Improvements in HbA1c with HTD1801 were parallelled with significant improvements in postprandial and fasting glucose at Week 24. In patients with mild renal impairment, HTD1801 improved eGFR, suggesting reno-protective potential. Significant reductions in lipids and inflammatory markers were also observed with HTD1801. Safety and tolerability were favorable and consistent with previous clinical trials of HTD1801. Serious AEs occurred in 4% vs 6% of patients with HTD1801 vs placebo, respectively. No patient experienced severe hypoglycemia during the study. An open-label extension is ongoing to confirm the durability of these benefits of HTD1801.

Abstract Title: Symphony 2: A Randomized, Placebo-Controlled Phase 3 Study of Berberine Ursodeoxycholate in Patients with Type 2 Diabetes Inadequately Controlled with Metformin
Presentation Number: 62
Presentation Date/Time: Tuesday September 16, 2025 / 2:45pm CEST
Format: Oral Presentation
Presenting Author: Linong Ji

“HTD1801 is an innovative small-molecule drug with a novel dual mechanism of action, simultaneously activating AMPK and inhibiting the NLRP3 inflammasome.”said professor Linong Ji, the leading principal investigator for this Phase 3 clinical trial and former Vice President of the International Diabetes Federation (IDF), Director of the Peking University Diabetes Center and Director of the Department of Endocrinology and Metabolism, Peking University People’s Hospital, “In completed Phase 3 clinical trials, it demonstrated consistent and clinically meaningful glucose-lowering effects with a favorable safety profile. Beyond glycemic control, HTD1801 has also shown multiple additional benefits, including lipid reduction, attenuation of inflammation, and improvements in renal function. As an orally administered antidiabetic agent, HTD1801 uniquely provides both cardiometabolic risk factor modification and renal protection, underscoring its substantial potential and competitive advantage for further clinical development.”

“The SYMPHONY 2 trial is our second Phase 3 study in type 2 diabetes to achieve its primary endpoint, underscoring the consistency and robustness of HTD1801’s clinical profile,” said Liping Liu, Founder, Chairwoman and CEO of HighTide Therapeutics. “We are particularly pleased that HTD1801 demonstrated not only glycemic benefit but potential cardiovascular and renal benefit in T2DM patients. With successful Phase 3 trials now in hand, we are well-positioned to submit our NDA in China later this year – marking a major step toward bringing a novel therapy to millions of patients who continue to face significant unmet needs in diabetes care.”

About HTD1801

HTD1801 is a first-in-class new molecular entity, addressing the residual risks of cardiovascular-kidney-metabolic (CKM) diseases. HTD1801 is an orally delivered, anti-inflammatory metabolic modulator that, as a single molecular entity, exhibits a unique dual mechanism of action through AMPK activation and NLRP3 inflammasome inhibition, both pathways working to mitigate dysfunctions associated with metabolic diseases. Multiple global clinical trial results have demonstrated comprehensive benefits of HTD1801, including improved insulin resistance, glycemic control, lipid lowering, renal benefit, weight loss, hepatic benefits, and anti-inflammatory effects. Therefore, HTD1801 has the potential to become a foundational CKM therapy.

About HighTide Therapeutics

HighTide Therapeutics, Inc. (2511.HK) is an innovative biopharmaceutical company specializing in metabolic diseases. The company is dedicated to developing first-in-class breakthrough therapies, providing therapeutic solutions with comprehensive benefits for patients worldwide. HighTide Therapeutics has established a globally positioned product pipeline with 100% self-developed intellectual property. The company has conducted clinical studies for multiple indications across various countries and regions, and the outcomes of these studies have been well recognized by global academic community and regulatory bodies worldwide. HTD1801, HighTide Therapeutics’ lead asset, is a first-in-class dual-target new molecular entity. It has received two Fast Track designations and one Orphan Drug designation from the US Food and Drug Administration (FDA), and has been included twice in the National Major Science and Technology Project for Significant New Drug Development in China.

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